Immune Profile Analysis in Peripheral Blood and Tumor in Patients with Malignant Melanoma.

Abstract

Melanoma is a severe and life-threatening malignancy derived from melanocytes. The traditional treatment for melanoma could not sustain satisfactory outcomes long term; however, the recent immune checkpoint treatment has made a breakthrough in these problems. Nivolumab is a representative immune checkpoint treatment, and this PD-1-targeted therapy has evolutionally developed and improved the clinical outcome in a recent decade. On the other hand, the clinical application of immune checkpoint treatment presents clinicians with novel questions, especially how to obtain additional efficacy and overcome the disadvantage by using this treatment. To answer these problems, we first investigated the distribution of PD-L1 in various organs to clarify the organs most affected by anti-PD-1 antibody treatment. Among various organs, lung, placenta, spleen, heart, and thyroid highly expressed PD-L1, while skin, thalamus, hippocampus, ovary, stomach, testis, and prostate showed lower expressions of PD-L1. Furthermore, the immune profiles were also examined in tumors and peripheral blood in patients with melanoma. PD-1 was highly expressed in CD8 and CD4 cells, and B cells also highly expressed PD-1 compared with NK cells. However, there was no significant difference in Th1/Th2/Th17 cytokines and inhibitory cytokine IL-10. Although nevus showed a low expression of PD-L1 compared with healthy skin, PD-L1 expression was increased in growth-phase melanoma. Finally, we analyzed the peripheral blood profiles in patients treated with nivolumab. PD-1-bearing dendritic cells (DCs) were increased during nivolumab treatment and Lin-CD11c+HLA-DR+ cells were highly increased during nivolumab treatment. These findings indicate a clue to answering the problems during nivolumab treatment and suggest to us the importance of multiple aspect observation during immune checkpoint treatment.